Inflammatory cytokines-induced beta-cell death and vacuole membrane protein 1 expression in -cells.

ARIOLFO, L; ANDREONE, L; GIMENO, ML; ROPOLO, A; ROSSI, M; VACCARO, MI; PERONE, MJ

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Lack of insulin production by means of destruction of -cells drive mainly by antigen specific T cells characterized type 1 diabetes. Autophagy is a highly conserved process of intracellular degradation and recycling pathway of dysfunctional organelles and proteins; it is crucial for maintaining cellular homeostasis as well as remodeling cellular components during normal development. Dysfunctions in this process have been associated with a variety of pathologies including cancer, neurodegenerative and inflammatory diseases, such as diabetes. We have found that in response to experimentally-induced diabetes by streptozotocin, the autophagy pathway was activated. VMP1 (vacuole membrane protein 1) is an autophagy-related protein that stimulates autophagosome formation, in association with Beclin-1, and was found elevated during the course of several pathologies, including experimental diabetes. Aim: Determine whether VMP1 is involved in -cell demise in the naturally occurring progress of disease employing the non-obese diabetic (NOD) mice, as a model of autoimmune diabetes. Methods: Female NOD mice (4-28wk); immuno-fluorescence (IF); cell culture. Results: Insulitis (immune cells infiltrating the islets) severity and VMP1 expression within -cells, increased with age in NOD mice while the intensity of immune-reactive insulin, assessed by IF decreased. Local production of inflammatory cytokines during insulitis triggers -cell death. Therefore, mimicking this process in vitro, we challenged the rat insulinoma INS-1E and isolated mouse islets with IL-1 + IFN- (CYT). We detected an increase in the expression of VMP1 in both INS-1E and -cells within islets after CYT exposure resembling those findings observed in islets from non-manipulated, naturally aged NOD mice.Discussion: VMP1 expression is induced by pro-inflammatory cytokines during the process of -cell dysfunction and death, occurring in autoimmune diabetes. Experiments are being carried out to unravel the mechanistic action of VMP1 in -cells under autoimmunity in diabetes.